NMR structure of the LCCL domain and implications for DFNA9 deafness disorder. Export

@article{citeulike:913578, abstract = {The LCCL domain is a recently discovered, conserved protein module named after its presence in Limulus factor C, cochlear protein Coch-5b2 and late gestation lung protein Lgl1. The LCCL domain plays a key role in the autosomal dominant human deafness disorder DFNA9. Here we report the nuclear magnetic resonance (NMR) structure of the LCCL domain from human Coch-5b2, where dominant mutations leading to DFNA9 deafness disorder have been identified. The fold is novel. Four of the five known DFNA9 mutations are shown to involve at least partially solvent-exposed residues. Except for the Trp91Arg mutant, expression of these four LCCL mutants resulted in misfolded proteins. These results suggest that Trp91 participates in the interaction with a binding partner. The unexpected sensitivity of the fold with respect to mutations of solvent-accessible residues might be attributed to interference with the folding pathway of this disulfide-containing domain.}, address = {Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden.}, author = {Liepinsh, E. and Trexler, M. and Kaikkonen, A. and Weigelt, J. and B\'{a}nyai, L. and Patthy, L. and Otting, G.}, citeulike-article-id = {913578}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/11574466}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=11574466}, day = {1}, issn = {0261-4189}, journal = {EMBO J}, keywords = {coch, dfna, domains, lccl}, month = {October}, number = {19}, pages = {5347--5353}, posted-at = {2006-10-26 14:55:11}, priority = {2}, title = {NMR structure of the LCCL domain and implications for DFNA9 deafness disorder.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11574466}, volume = {20}, year = {2001} }

TY - JOUR ID - citeulike:913578 L3 - citeulike-article-id:913578 N2 - The LCCL domain is a recently discovered, conserved protein module named after its presence in Limulus factor C, cochlear protein Coch-5b2 and late gestation lung protein Lgl1. The LCCL domain plays a key role in the autosomal dominant human deafness disorder DFNA9. Here we report the nuclear magnetic resonance (NMR) structure of the LCCL domain from human Coch-5b2, where dominant mutations leading to DFNA9 deafness disorder have been identified. The fold is novel. Four of the five known DFNA9 mutations are shown to involve at least partially solvent-exposed residues. Except for the Trp91Arg mutant, expression of these four LCCL mutants resulted in misfolded proteins. These results suggest that Trp91 participates in the interaction with a binding partner. The unexpected sensitivity of the fold with respect to mutations of solvent-accessible residues might be attributed to interference with the folding pathway of this disulfide-containing domain. IS - 19 JF - EMBO J SN - 0261-4189 AD - Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden. EP - 5353 TI - NMR structure of the LCCL domain and implications for DFNA9 deafness disorder. VL - 20 SP - 5347 KW - coch KW - dfna KW - domains KW - lccl AU - Liepinsh, E AU - Trexler, M AU - Kaikkonen, A AU - Weigelt, J AU - Bányai, L AU - Patthy, L AU - Otting, G PY - 2001/10/01/ UR - http://view.ncbi.nlm.nih.gov/pubmed/11574466 ER -